In an international publication, WO 97/29102 is disclosed a quinolonecarboxylic acid having a cyclopropyl group at the 1-position, an isoindolinyl group at the 7-position and a difluoromethoxy group at the 8-position, which is a synthetic antibacterial agent.
However, in the production method of the quinolonecarboxylic acid described in the above laid-open patent publication, 2,6-difluoroaniline which is difficult to synthesize and procure industrially, must be used as a starting material; many steps are employed; explosive sodium azide is used; and a diazotization step of low productivity is included. Thus, in carrying out the industrial production of the quinolonecarboxylic acid according to above method, there have been many problems in cost and safety.
The present inventors made studies on the intermediate for the quinolonecarboxylic acid and the process for production thereof. As a result, it was found out that by using a 2-difluoromethoxy-3-halognonitrobenzene (which is a novel substance) as a raw material, reducing the compound to corresponding aniline, subjecting the aniline to cyclopropylation to synthesize an N-cyclopropylaniline, and reacting it with a dialkyl alkoxymethylenemalonate typified by diethyl ethoxymethylenemalonate, a corresponding adduct was formed.
By subjecting the adduct to a ring-closing reaction according to a known method, there can be easily derived a precursor of the above-mentioned quinolonecarboxylic acid, i.e. an alkyl 1-cyclopropyl-4-oxo-7-halogeno-8-difluoro-methoxy-3-carboxylate. Therefore, it was confirmed that the above-mentioned intermediates (2-difluoromethoxy-3-halogenonitrobenzene, corresponding aniline and N-cyclopropylaniline) are important novel compounds in producing the above quinolonecarboxylic acid derivative at a low cost according to an industrially satisfactory method and are all easily synthesized industrially. Thus, the present invention has been completed.